J Clin Gastroenterol. 2025 Feb 17. doi: 10.1097/MCG.0000000000002149. Online ahead of print.

Erin Mauney ¹, Franklin King 4th ², Helen Burton-Murray ³, Braden Kuo ³

Author information

¹Pediatric Gastroenterology and Nutrition Program, Massachusetts General Hospital for Children.

²Center for the Neuroscience of Psychedelics.

³Center for Neurointestinal Health, Massachusetts General Hospital, Harvard Medical School, Boston, MA.

Abstract

Irritable bowel syndrome (IBS) is prevalent and can be disabling. Many patients remain symptomatic despite behavioral and medical therapies. Psychedelic-assisted therapy (PAT), in which serotonergic agents like psilocybin are administered in a psychotherapeutic context, has shown promise for refractory psychiatric disorders, including major depressive disorder and post-traumatic stress disorder. Emerging evidence suggests PAT may also be beneficial for chronic pain conditions, including fibromyalgia, low back pain, and migraines. IBS is highly comorbid with depression, anxiety, and other chronic pain disorders, suggesting shared cognitive and neurological roots and potentially shared therapeutic targets. In this editorial, we discuss 3 lines of evidence for PAT as a treatment for IBS, under the overarching themes of (1) psychological mechanisms (the findings from historic studies of psychedelics for chronic pain and the elements of psychobiological dysfunction targeted by PAT), (2) central nervous system mechanisms (default mode network modulation and induction of neuroplasticity), and (3) the neurointestinal pathophysiology of IBS that may be modified by PAT. We argue that this evidence suggests PAT is worthy of study as a new therapy for IBS, and potentially for other disorders of gut-brain interaction (DGBI). Successful application of PAT to gastrointestinal disease would represent a major step beyond mind-body dualism, with potential implications for other functional somatic disorders.